EElectrochemical signals in living organisms are governed by the difference of ions across the plasma membrane and are mediated by proteinaceous molecular structures called ion channels. Ion channels can be of different types based on how it gets triggered. One of the broadly classified and well-studied ion channels is Voltage-Gated Ion Channels (VGIC). Different types of VGICs exist based on the ions they conduct. One of the major classes of VGIC which plays an important physiological role is Voltage-Gated Potassium (Kv) Channels. Based on the sequence homology eight different types of voltage-gated potassium (Kv) shaker-related channel subfamilies have been identified: Kv1-Kv6 and Kv8-Kv9. Surprisingly, subfamilies of Kv1- Kv4 not only oligomerize to form homo-tetramers but can also form hetero-tetramers increasing the diversity of the Kv channel complex. Meanwhile, the members of the Kv5, Kv6, Kv8, and Kv9 subfamilies are unable to form functional channels even though they possess the typical topology of the Kv alpha subunit. Therefore, they have been designated as Silent Kv (KvS) subunits. KvS interacts with the members of the Kv2 subfamily forming Kv2/KvS hetero-tetramers which show unique biophysical properties. Structurally, the Kv channel comprises four alpha subunits arranged around a central pore. Individual alpha subunit comprises six transmembrane segments S1-S6 with a cytoplasmic N and C terminal. The T1 domain present in the N-terminus of each subunit facilitates the assembly of the alpha subunit into a fully functional channel. Being homo and hetero-tetrameric the individual alpha subunit shows macroscopic cooperativity for the activation (opening) of the channel. Studying such biophysical property subunit concatenation is a powerful tool. It allows one to manipulate individual subunits once at a time. In a recent study from our laboratory, it had been reported in ligand-gated CNG channels about subunit contribution in the process of activation using subunit concatenation, electrophysiology, and Hidden Markov Modeling. Based on the earlier finding we now try to understand the activation process of the VGIC by exploiting the above-mentioned technique.